Lyme disease is the most prevalent tick-borne disease in the northern hemisphere with many endemic areas in Europe and around the world. The disease is a multi-system spirochetosis with dermatologic, neurologic and rheumatological manifestations. Borrelia burgdorferi regulates genes in response to a number of environmental signals such as temperature and pH. These differences in culture conditions are reflective of the alterations that the spirochete would experience during the infectious cycle from tick (23C, pH 8.0) to mammal (35C, pH 7.0). Additional genes regulated by environmental cues have been identified and partially characterized with little insight into their precise role in this important adaptation. It is theorized, however, that the genes differentially expressed in such a fashion may provide important clues to important virulence determinants. These studies have been set up to explore these possibilities. Central to these studies, however, is the need for and development of a reliable, stable, easily assayed reporter system in Borrelia burgdorferi.